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Cell Biology International (2007) 31, 856859 (Printed in Great Britain)
Substance P enhances soluble ICAM-1 release from adult rat cardiac fibroblasts by a p42/44 MAPK- and PKC-mediated mechanism
S. Sapna and K. Shivakumar*
Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 011, Kerala, India
Substance P, a pro-inflammatory neuropeptide, is released from cardiac peptidergic nerves under conditions like ischemia but whether it modulates inflammatory processes in the heart remains unexplored. This study demonstrates for the first time that substance P augments the production of the soluble form of intercellular adhesion molecule-1, sICAM-1, by adult rat cardiac fibroblasts. However, RT-PCR showed no concomitant increase in ICAM-1 transcript levels, suggesting that the increase in sICAM-1 may involve post-transcriptional/translational mechanisms. Use of pharmacological inhibitors revealed that the stimulatory effect of substance P on sICAM-1 production is mediated by p42/44 MAPK and protein kinase C. Preliminary experiments also showed that the neuropeptide stimulates the production of prostaglandin E
Key words: Cardiac fibroblasts, Substance P, sICAM-1, p42/44 MAPK, Protein kinase C.
*Corresponding author. Tel.: +91 471 2524593; fax: +91 471 2446433.
Received 22 November 2006/4 January 2007; accepted 18 January 2007doi:10.1016/j.cellbi.2007.01.031